Norovirus capsid and rotavirus VP6 protein for use as combined vaccine

Abstract

The present invention relates to a combined norovirus and rotavirus vaccine for prevention of norovirus and rotavirus infection and/or viral-induced diarrheal and vomiting diseases in man. More specifically, the invention comprises a method of preparing combination vaccine compositions comprising norovirus and rotavirus antigens, in particular mixtures of norovirus VLPs and rotavirus recombinant VP6 protein or double-layered VP2/VP6 VLPs. In addition, the invention relates to methods of inducing an immune response.

The invention claimed is: 
     
       1. An immunogenic composition comprising at least one norovirus VLP comprising a norovirus GII-4 VLP, and at least one rotavirus VP6 antigen. 
     
     
       2. The immunogenic composition according to  claim 1 , further comprising a norovirus antigen selected from the group consisting of antigenic capsid peptides, and antigenic capsid proteins. 
     
     
       3. The immunogenic composition according to  claim 1 , wherein said GII-4 VLP is monovalent. 
     
     
       4. The immunogenic composition according to  claim 1 , wherein more than one type of norovirus VLP is present in the immunogenic composition. 
     
     
       5. The immunogenic composition according to  claim 1 , wherein said rotavirus VP6 antigen is selected from the group consisting of recombinant VP6 (rVP6) protein, double-layered VP2/VP6 VLP, VLPs comprising VP6 protein, and any combinations thereof. 
     
     
       6. The immunogenic composition according to  claim 5 , wherein said rVP6 protein is in a multimeric form selected from the group consisting of tubules, spheres, sheets, and any combinations thereof. 
     
     
       7. The immunogenic composition according to  claim 1 , further comprising a sterile, nontoxic pharmaceutically acceptable physiological carrier. 
     
     
       8. The immunogenic composition according to  claim 1 , wherein the immunogenic composition is capable of inducing an immune response that inhibits at least one member selected from the group consisting of: norovirus and rotavirus infections, norovirus and rotavirus induced diarrheal and vomiting diseases, and norovirus and rotavirus induced gastroenteritis. 
     
     
       9. A method comprising administering the immunogenic composition according to  claim 1 , to a subject in need thereof to induce an immune response to inhibit at least one member selected from the group consisting of: norovirus and rotavirus infections, norovirus and rotavirus induced diarrheal and vomiting diseases, and norovirus and rotavirus induced gastroenteritis. 
     
     
       10. A method of producing the immunogenic composition according to  claim 1 , comprising
 a) co-expressing at least one norovirus GII-4 VLP and at least one rotavirus VP6 protein in a cell culture, and 
 b) isolation the VLP and VP6 proteins from the cell culture. 
 
     
     
       11. The method according to  claim 10 , wherein said norovirus and rotavirus proteins are produced in recombinant baculovirus-infected insect cells. 
     
     
       12. A method of producing the immunogenic composition according to  claim 1 , comprising the steps of:
 a) producing a norovirus GII-4 VLP in cell culture, isolating the VLP, and purifying the VLP; 
 b) producing a rotavirus VP6 protein in cell culture, isolating the VP6 protein, and purifying a rotavirus VP6 protein; and 
 c) mixing said norovirus VLP and rotavirus VP6 proteins. 
 
     
     
       13. The method according to  claim 12 , wherein said norovirus and rotavirus proteins are produced in recombinant baculovirus-infected insect cells.